Early signs of architectural and biomechanical failure in isolated myofibers and immortalized myoblasts from desmin-mutant knock-in mice

Journal article


Publication Details

Author(s): Diermeier S, Iberl J, Vetter K, Haug M, Pollmann C, Reischl B, Buttgereit A, Schürmann S, Spörrer M, Goldmann W, Fabry B, Elhamine F, Stehle R, Pfitzer G, Winter L, Clemen CS, Herrmann H, Schröder R, Friedrich O
Journal: Scientific Reports
Publication year: 2017
Volume: 7
Journal issue: 1
Pages range: 1391
ISSN: 2045-2322


Abstract


In striated muscle, desmin intermediate filaments interlink the contractile myofibrillar apparatus with mitochondria, nuclei, and the sarcolemma. The desmin network's pivotal role in myocytes is evident since mutations in the human desmin gene cause severe myopathies and cardiomyopathies. Here, we investigated skeletal muscle pathology in myofibers and myofibrils isolated from young hetero- and homozygous R349P desmin knock-in mice, which carry the orthologue of the most frequent human desmin missense mutation R350P. We demonstrate that mutant desmin alters myofibrillar cytoarchitecture, markedly disrupts the lateral sarcomere lattice and distorts myofibrillar angular axial orientation. Biomechanical assessment revealed a high predisposition to stretch-induced damage in fiber bundles of R349P mice. Notably, Ca(2)(+)-sensitivity and passive myofibrillar tension were decreased in heterozygous fiber bundles, but increased in homozygous fiber bundles compared to wildtype mice. In a parallel approach, we generated and subsequently subjected immortalized heterozygous R349P desmin knock-in myoblasts to magnetic tweezer experiments that revealed a significantly increased sarcolemmal lateral stiffness. Our data suggest that mutated desmin already markedly impedes myocyte structure and function at pre-symptomatic stages of myofibrillar myopathies.



FAU Authors / FAU Editors

Buttgereit, Andreas Dr.
Lehrstuhl für Medizinische Biotechnologie
Fabry, Ben Prof. Dr.
Lehrstuhl für Biophysik
Friedrich, Oliver Prof. Dr. Dr.
Lehrstuhl für Medizinische Biotechnologie
Goldmann, Wolfgang Prof.
Professur für Biomedizinische Physik
Haug, Michael
Lehrstuhl für Medizinische Biotechnologie
Iberl, Julian
Lehrstuhl für Prozessmaschinen und Anlagentechnik
Meyer, Charlotte
Lehrstuhl für Medizinische Biotechnologie
Reischl, Barbara
Lehrstuhl für Medizinische Biotechnologie
Schröder, Rolf Prof. Dr.
Professur für Neuropathologie
Schürmann, Sebastian Dr. rer. nat.
Lehrstuhl für Medizinische Biotechnologie
Spörrer, Marina
Professur für Biomedizinische Physik
Menacher, Karoline
Lehrstuhl für Kunststofftechnik


How to cite

APA:
Diermeier, S., Iberl, J., Vetter, K., Haug, M., Pollmann, C., Reischl, B.,... Friedrich, O. (2017). Early signs of architectural and biomechanical failure in isolated myofibers and immortalized myoblasts from desmin-mutant knock-in mice. Scientific Reports, 7(1), 1391. https://dx.doi.org/10.1038/s41598-017-01485-x

MLA:
Diermeier, Stefanie, et al. "Early signs of architectural and biomechanical failure in isolated myofibers and immortalized myoblasts from desmin-mutant knock-in mice." Scientific Reports 7.1 (2017): 1391.

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Last updated on 2018-19-04 at 04:12